Hallucinogens: mechanisms and medical complications

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https://hdl.handle.net/2144/12070

Abstract

Hallucinogens are drugs that alter consciousness by distorting primarily auditory and visual perception but they can affect any sensory system. Hallucinogens also affect judgment, orientation, memory, or emotion. Despite the profound alteration in perception, adverse effects are minimal and hallucinogens are not addictive. Hallucinogen use has its roots in shamanic practices of indigenous cultures and is even incorporated in today’s religions like the Native American Church. By putting a person in an altered state of consciousness, many religions believed that the user was able to see beyond the boundaries of reality and reach out to mythical beings. Hallucinogen use in scientific research was not popular until the 1950’s when Albert Hoffman discovered lysergic acid diethylamide (LSD). The discovery of drug encouraged further research into understanding its mechanisms and its relationship with mental diseases like schizophrenia. Unfortunately, the Comprehensive Drug Abuse Prevention and Control Act of 1970 significantly limited hallucinogenic research and human
research for the last 42 years. However, animal research in the last 20 years has determined the importance of serotonergic mechanisms and more specifically the 5-HT2A receptors in mediating LSD’s hallucinogenic effects. Researchers continue to identify mechanisms of LSD action. In addition to serotonergic actions, LSD is active with dopaminergic and metabotropic glutamate receptors. PET scans and fMRI’s have also revealed the importance of the prefrontal cortical region and its interaction with other areas during a hallucinogenic state. The relationship between LSD and acute psychosis is also being explored via animal models. Although human clinical research is limited, recent research sees a much deeper relationship by linking LSD brain activity and neurotransmitter levels to psychotic behaviors. This further understanding of hallucinogens on a physiological and psychological level has led to possible psychotherapeutic areas of research in anxiety and substance abuse. This thesis describes a brief history of hallucinogenic research, the pharmacology and neuroanatomy of serotonergic hallucinogens, the acute and chronic adverse effects of serotonergic hallucinogens, the possible treatments for complications of hallucinogens, the epidemiology, the relationship between hallucinogens and schizophrenia, and possible therapeutic uses of serotonergic hallucinogens.
With its minimal adverse effects in humans and its powerful influence on the human psyche, serotonergic hallucinogens are invaluable tools for understanding the human mind.